tbuckley/cabot-search huggingface dataset:
Altmetrics of breast cancer clinical trials’ subgroup analysis: A systematic review.
Authors: Nada Wael Odeh, Marah Alzubi, Jawad Alrawabdeh, Muntaser Al Zyoud, Yazan Hamadneh, Samer Al Hadidi
Journal: Journal of Clinical Oncology (2023)

e13640 Background: Sharing findings of clinical trials using the internet and social media is increasing. Altmetric attention scores are instantaneous evaluations of the influence and popularity of science in a variety of media, such as news, blogs, and different social media platforms. Altmetrics’ distributions and trends for subgroup analyses were not previously investigated. Our study aimed to characterize altmetrics of the studies reporting subgroup analyses of breast cancer clinical trials and to assess the association between altmetrics and other characteristics of publications. Methods: We performed a systematic review of all published secondary analyses of breast cancer clinical trials form Jan 2020 until Feb 15, 2022. 1491 secondary analysis of solid malignancies were identified of which 287 were related to breast cancer. The altmetric scores for the included studies were obtained from a website named Bookmarklet for Researchers on the 12 th of Feb 2023. Pearson’s correlation, Independent Samples t test, the one-way analysis of variance (ANOVA), and Chi-Square test were utilized to identify associations between a number of the studies’ characteristics and altmetrics. Statistical analysis was completed using SPSS Statistics. Results: Altmetric scores were captured for 211 (73.5%) of the 287 included publications. The median score was 4 (IQR 2-19). The captured altmetric scores ranged from 1 to 882. Around 45% of the included studies were first-authored by women and pharmaceutical companies funded approximately 35%. Both gender and funding source did not show any effect on the altmetric scores. Higher altmetric scores ( &gt; = 4) were associated with authors who reported conflicts of interest (COI) (P = 0.001), studies published in 2015 or after (P = 0.003), papers published in journals with higher impact factors (P &lt; 0.001), and publications with a higher number of authors (P = 0.019). Conclusions: Higher number of authors, presence of COI, higher impact factor of the publishing journal, and a publication year of 2015 or after are associated with higher altmetric scores in subgroup analyses of breast cancer-based clinical trials. Given the observational nature of secondary analysis and possible inaccurate conclusions, caution must be entertained when interpreting their findings.
A phase Ib/II study to evaluate surufatinib combined with camrelizumab and chemotherapy in the second-line treatment of advanced colorectal cancer: Phase Ib results.
Authors: Sheng Li, Liangjun Zhu, Xiaoyou Li, Jiayuan Huang, Jun Bao
Journal: Journal of Clinical Oncology (2023)

3555 Background: Surufatinib is a novel small-molecule kinase inhibitor targeting VEGFR1-3, FGFR and CSF-1R with confirmed efficacy in epNET and pNET. Preclinical studies have demonstrated that surufatinib combined with immune checkpoint inhibitors (ICIs) have synergistic antitumor effects by modulating tumor immune microenvironment. Additionally, surufatinib plus toripalimab (anti-PD-1) has showed preliminary anti-tumor activity in multiple solid tumors, including colorectal cancer (CRC). This study aimed to evaluate the efficacy and safety of surufatinib plus camrelizumab (anti-PD-1), irinotecan and GM-CSF as second-line treatment in advanced CRC. Here we reported the results of the phase Ib study. Methods: This ongoing phase Ib/II, open-label trial (NCT04929652) enrolled patients (pts) aged 18-75 years old with pathologically confirmed locally advanced or metastatic CRC who have progressed on/been intolerant to the standard first-line therapy. In the Ib dose escalation/de-escalation phase, pts received surufatinib at 250mg once daily (QD) as starting dose, in combination with fixed dose of camrelizumab (200 mg, d1), irinotecan (200 mg/m 2 , d1) and GM-CSF (5ug/kg, d2-d7), every 3 weeks (Q3W). Based on DLTs, the dose of surufatinib should escalate to 300 mg or de-escalate to 200 mg. The primary objective of the phase Ib study was to determine the safety and DLT in first treatment cycle defining the recommended phase 2 dose (PR2D). Additional 36 pts were enrolled in the phase II dose expansion stage using RP2D. Primary endpoint of phase II was ORR as per RECIST 1.1. Secondary endpoints included PFS, DCR, OS and safety. Results: Enrollment opened in Nov 2021 and data cutoff in Dec 2022. 12 pts (median age 54) were treated in Phase Ib study (surufatinib 250 mg: N = 6; surufatinib 300 mg: N = 6). 75% were male and 17% had ECOG PS 1. 11/12 (92%) pts were positive for KRAS, NRAS or BRAF mutations. No DLT was observed in the starting dose cohort (surufatinib 250 mg), and one patient in the surufatinib 300 mg cohort experienced DLT (Grade [G] 3 vomiting). Surufatinib 300 mg QD was defined as the RP2D. Other G3 treatment related adverse events (TRAEs) were hypertension (1/12; 8.3%) and diarrhea (1/12; 8.3%). All other TRAEs were grade 1-2, and the most common (≥40%) were diarrhea (75%), fatigue (58%), vomiting (58%), nausea (50%), hypertension (42%), proteinuria (42%) and alopecia (42%). Of the 12 pts evaluable for tumor response, 3 pts achieved PR, 9 pts achieved SD. The ORR was 25% (3/12), the DCR was 100% (12/12) and median PFS was 7.2 months (95%CI 3.7-10.7). Conclusions: Surufatinib plus camrelizumab, irinotecan and GM-CSF was well tolerated, with a manageable safety profile, and showed preliminary anti-tumor activity in patients with advanced CRC. The dose-expansion phase is ongoing. Clinical trial information: NCT04929652 .
Better together: A team-based approach to improve prior authorization efficiencies and wellness in physicians and advanced care providers.
Authors: Sofya Pintova, Jessica Royer, Tianxiang Sheng, Mark Liu, Alana Noble-Kirk, Cardinale B. Smith, Aarti Sonia Bhardwaj
Journal: Journal of Clinical Oncology (2023)

e13664 Background: The burden of prior authorizations (PAs) required for costly oncologic treatments is high. Upon PA denials, peer-to-peer requests are performed. These requests consume time and effort of physicians and advanced care providers (APPs) contributing to burnout and may have a negative impact on patient care. We aimed to assess the degree to which the PA process contributed to burnout among oncology clinicians prior to implementation of a new streamlined workflow aimed at improving clinician wellness. Methods: A baseline wellness survey was sent to all hematology-oncology faculty and APPs at the largest clinical site of our academic cancer center. Burn out, our primary outcome, was measured using the work-related Copenhagen Burnout Inventory. We included selected questions from the American Medical Association (AMA) surveys regarding physician perceived impact of PAs on clinical workload and care delivery. We asked physicians and APPs to rate the impact of PAs on burnout on a scale of 0-100. Analysis was conducted using descriptive statistics. This study was sponsored by our Office of Well-Being and Resilience. Results: The wellness survey was completed by 35 physicians and 21 APPs with a response rate of 53% in both. The median Copenhagen burnout score for physicians was 46.43 (35.71-60.71) with higher burn out scores among those identifying as females, in practice less than 15 years and with more than 60% time in direct patient care. The median burn out score for APPs was 64.28 (50-83.03). Similar to physicians, APPs with less clinical experience had higher burn out scores. When asked about the impact of PAs on burnout on a scale of 0-100, physicians at the main site reported a median of 13.5, while APPs reported a median of 53.5. Conclusions: Physicians and APPs report noteworthy baseline rates of burnout and dedicate a significant portion of the week to completing PAs. Importantly, APPs perceived the PAs to have a high impact on their burn out compared to physicians. We will use these data to determine the efficacy of a new process that utilizes a single EMR platform for finance and cancer registry teams to abstract and document all of the required elements to streamline the PA process for intravenous/injection cancer treatments with the goal to reduce the number of PAs and improve wellness. [Table: see text]
Network-enabled rapid growth of a US-based remote asynchronous oncology subspecialist case review service.
Authors: Howard Jack West, Debra A. Wong, Nitya Nathwani, Carol Wright, Crystal Liang, Todd M. Sachs, Afsaneh Barzi
Journal: Journal of Clinical Oncology (2023)

e13507 Background: AccessHope (AH) is a company that provides remote subspecialist insight on cancer care for patients via an asynchronous model of review of medical records followed by a detailed assessment of current and potential future management options sent to the patient’s local oncologist. This summary characterizes the rapid and ongoing scaling and growth as demand for this service has expanded and as AccessHope has transitioned from a single site to a geographically diverse US-based network of National Cancer Institute-designated comprehensive cancer centers (NCI-CCCs) as foundational partners. Methods: Cases were identified based on a trigger list of high complexity cancers or by request for case review by participating patients with cancer. Using descriptive statistics, we assessed measures of eligible patient, completed case volumes, and number of unique expert reviewers over time; the distribution of cancer types; the extent of concordance between care outlined by the local care team and that recommended by the reviewing expert; and potential cost savings from recommended changes. Results: From 1/2019-9/2022, the number of sponsor organizations and eligible “covered lives” increased by 1462% and 393% respectively; case volume increased from 42 to 525 cases/quarter over this interval. The most common cancer diagnoses were gastrointestinal (30%), hematologic/lymphoid (18%), lung (14%), and breast (12%). While reviewers recommended an alternative treatment in 29% of cases and agreed overall with current management in 71%, only 4% agreed and had no proposed refinements associated with anticipated evidence-based improvements. Recommendations leading to cost savings if adopted were identified in 16.1% of cases, translating to projected cost savings of $13,008/patient. Conclusions: After initially demonstrating the feasibility of completing a rapid turnaround of cases of lung cancer either patient-initiated for review or prospectively triggered by diagnosis and stage, this program of asynchronous second opinions has grown from a single institution to a network of five NCI-CCCs around the US. Demand for this service has rapidly escalated, so that AH has been able to provide input and support to local oncologists for many-fold more physicians and patients over the past few years.
Androgen receptor expression in female patients with triple-negative breast cancer: Relation to clinical, pathological, and ethnical data and comparison with non–triple-negative breast cancer.
Authors: Jamal Zidan
Journal: Journal of Clinical Oncology (2023)

e13022 Background: Breast cancer is the most common tumor among women. It constitutes 33% of all tumors in women in Israel. In addition to stage of the disease, other detective factors such as estrogen and progesterone receptors (ER) (PR), Human epidermal growth factor receptor 2 (HER2) and proliferation index (KI67) are examined to determine the treatment for metastatic disease and for the adjuvant therapy. Despite a good prognosis of breast cancer about 10-15% of breast tumors do not contain ER, PR, HER2. This group of is more, aggressive, called Triple negative (TN) tumor. In TN tumors the treatment is mainly chemical therapy, and the survival is lower than other types (Non triple negative: NTN) of breast cancers. Androgen receptor (AR) receptor is very important in prostate cancer and forms the basis of hormonal treatments for prostate cancer. AR can also be present in some breast cancer patients. This study examined AR levels in patients with TN breast cancer in order to evaluate whether AR could be used as a prognostic or therapeutic factor in patients with TN breast cancer. Methods: Demographic, clinical and pathological data were collected from the files of breast cancer patients treated at the Oncology Institute at Ziv Medical Center, Israel, between 2013 and 2020. Tissue samples were taken from the tumors at the Ziv Pathological Institute which were stored in paraffin. The evaluation of AR in breast cancer tissues was done by immunohistochemistry test. 55 TN cases were examined along in addition 90 cases with NTN were examined for comparison. Results: The mean age of the patients in the TN group was 56.9 ± 16.2 compared with 59.8 ± 13.5 years in the NTN group. 83.6% were Jewish and 16.4% Arab. 36.4% of TN patients were of childbearing age. 61.8% of the tumors in TN were Grade 3 compared to 32.2% in the NTN group (P = 0.001). Ki67) was 57.4 ± 27.8 in TN tumors and 24.9 ± 25.4 in NTN (0.001 &lt;P =). In 69.1% of TN patients AR was found to be negative compared to 26.7% in NTN (P = &lt;0.001). AR was found to be high in 9% of TN patients and in 72.8% in NTN who survived 5 years without disease (P = &lt;0.001). Negative AR was found in 75% of the patients who died from the disease in both groups. Positive AR was found in 30.9% of TN tumors compared to 73.3% in NTN (P = &lt;0.001). Conclusions: The AR receptor has a prognostic importance in breast cancer. We found that positive AR is more common in NTN patients than in TN. Survival of patients with low expression of AR is lower. The test is also relatively inexpensive, and it could be possible to be checked in all patients with TN breast cancer all over the hospitals. On the basis of the recent results, we suggest performing a new multicenter study for the treatment of AR-positive TN patients who failed conventional therapies with AR based hormone therapy.
The antinociceptive effects of selective TRPV1 antagonist RCI002 against chemotherapy-induced peripheral neuropathy.
Authors: Minjung Kim, Juil Park, Harith Hasrul, Sung Taek Park, Yong Ho Kim
Journal: Journal of Clinical Oncology (2023)

e15111 Background: Chemotherapy-induced peripheral neuropathy (CIPN) is a common side effect experienced by cancer patients receiving chemotherapy. Recent reports showed that transient receptor potential (TRP) channels are involved in paclitaxel- or oxaliplatin-induced neuropathic pain. TRP vanilloid 1 (TRPV1) may contribute to the development of mechanical allodynia and thermal hyperalgesia after cisplatin or oxaliplatin treatment. Moreover, paclitaxel-induced behavioral hypersensitivity is prevented and reversed by administration of TRPV1 antagonists. RCI002 is a potent and selective TRPV1 antagonist, blocking capsaicin activation of the target, with a little affect pH or heat activation. We found that RCI002 relieves neuropathic pain by inhibiting TRPV1, an important nociceptor involved in pain signal transduction, and does not cause thermoregulation, a problem with existing TRPV1 antagonists. In this study, Calcium imaging and patch clamp were employed to examine effects of RCI002 on mouse dorsal root ganglion (DRG) neurons and HEK293t cells expressing TRPV1. We also investigated RCI002 associated paclitaxel-induced peripheral neuropathic pain using a rat model. Methods: Dorsal root ganglion (DRG) neurons and TRPV1-transfected human embryonic kidney-derived (HEK) 293 cells were used for calcium imaging or whole-cell patch-clamp recording. CIPN was induced by intraperitoneal administration of paclitaxel 2 mg/kg for 4 consecutive days using adult male Sprague-Dawley rats. RCI002 were administered intraperitoneal and the paw withdrawal thresholds were measured using von Frey filaments. Results: We previously showed that RCI002, a novel TRPV1 antagonist that could be referred to as a new class of TRPV1 modulators that produce a significant analgesic effect formalin-induced behavior and improved mechanical allodynia undergoing spinal nerve ligation(SNL) in rats without hyperthermic effect. In the present study, The selective TRPV1 inhibitor RCI002 impaired capsaicin-induced calcium influx in DRG neurons. hTRPV1 expressed in HEK293 cells mediated a hemin-induced calcium influx which was blocked by RCI002. Behavioral assessment using the von Frey filaments. SD rat that received paclitaxel developed mechanical hypersensitivity to Von Frey filament stimulations of their hindpaws. Paclitaxel-induced hypersensitivity inhibited by TRPV1 antagonist RCI002(RCI002 EC50 = 0.85mg/kg). RCI002 significantly increased the paw withdrawal threshold more than pregabalin in CIPN rats(Pregabalin EC50 = 14.77mg/kg). Conclusions: Our findings suggest that RCI002 may be a promising approach to reduce paclitaxel-induced hyperexcitability and thereby to reduce neuropathy pain.
Alternative trastuzumab dosing schedules and association with health care greenhouse gas emissions.
Authors: Garth William Strohbehn, Sofia Jacobson, Alec Kacew, Randall W. Knoebel, Po-Hung Hsieh, Mark J. Ratain
Journal: Journal of Clinical Oncology (2023)

e13644 Background: Climate change due to greenhouse gas (GHG) emissions by humans imperils health. Health care is a major source of GHG emissions and thus reducing health care’s environmental impact should be a global priority. GHG emissions associated with the production and administration of cancer drugs, as well the downstream societal costs in human health terms, are undescribed. The extent to which a given cancer drug’s dosing frequency and duration impact GHG emissions is unknown. Methods: Using trastuzumab for HER2-positive breast cancer as a use case, we conducted a case-control simulation study of single, U.S. academic medical center data to estimate the expected reductions in GHG emissions with three alternative dosing strategies (6-month adjuvant treatment duration, extended-interval dosing, and both) using streamlined life-cycle analysis. We estimated the per-patient relative reduction in GHG emissions expected to occur with each of the alternative dosing strategies and, in exploratory analysis, the societal health costs ( e.g., disability-adjusted life-years [DALYs] and excess mortality per kg CO 2 ) associated with therapy-related GHG emissions, using conventional versus alternative dosing strategies. Results: Adoption of 6-month adjuvant trastuzumab reduced expected per-patient GHG emissions in the adjuvant setting by 10%. Adoption of both 6-month adjuvant trastuzumab and pharmacokinetically-supported every 4-week trastuzumab dosing reduced GHG emissions by 4.5%, 18.7%, and 14.6% in the neoadjuvant, adjuvant, and metastatic settings, respectively. An estimated 8.1 DALYs and 4.6 excess lives are lost annually worldwide as a result of U.S.-based administration of conventionally dosed trastuzumab. Adoption of alternative dosing in the U.S. is estimated to enable avoidance of approximately 1.5 DALYs and 0.9 excess lives lost annually. Conclusions: Alternative dosing strategies, suggested to be noninferior by pharmacokinetic and clinical evidence, are estimated to reduce the societal health costs imposed on bystanders that arise from cancer care’s environmental impact. Environmental impact and its resultant societal health costs should be considered in clinical trial design, re-interpretation of previously conducted trials, regulatory decision-making, and health technology assessments of both new and existing cancer therapies.
Decreasing the burden of febrile neutropenia through dynamic remote patient monitoring: The DEFeNDER program.
Authors: Joshua Pritchett, Jonas Paludo, Qian Shi, Nandita Khera, Zachary Yetmar, John W. Wilson, Rozalina McCoy, Angela Leuenberger, Sarah Phillips, Kristina Pearson, Samantha McColley, Robert Haemmerle, Lindsey R. Sangaralingham, Alexander J. Ryu, David Phelan, Naseema Gangat, Julian R. Molina, Jon Charles Tilburt, Bijan J. Borah, Tufia C. Haddad
Journal: Journal of Clinical Oncology (2023)

1535 Background: Ambulatory management of select patients with febrile neutropenia (FN) may substantially decrease patients’ burden of illness and improve their quality of life, and is recommended by American Society of Clinical Oncology (ASCO) guidelines. However, in the United States, inpatient management remains the universal standard. We hereby report the health care utilization associated with the DEFeNDR remote patient monitoring (RPM) program, which leverages technology and virtual centralized nurse monitoring to facilitate ambulatory management of FN as an alternative to hospital-based care. Methods: Adult patients with cancer hospitalized with FN were assessed daily for eligibility to participate in the DEFeNDR program. Eligibility criteria included MASCC score &gt;21 (per ASCO guidelines), and clinical judgment of the attending provider. Patients receiving cellular therapy (CAR-T, BMT) in the prior 100 days were excluded. Eligible patients agreeing to participate in the 30-day program were provided a kit containing cellular-enabled, pre-connected devices to facilitate monitoring, including twice-daily vital signs and electronic symptom questionnaires. Data were EHR-integrated in real-time and embedded decision trees facilitated alerts for adverse trends. RPM nurses responded to alerts and escalated care as indicated by pre-specified care pathways. Program assessment was performed at 20 weeks after full implementation. The primary outcome was the mean proportion of evaluable days spent inpatient (mPEDI) within 30 days of eligibility compared between those who participated in the program vs. those who declined. Results: 35 patients were offered participation in the DEFeNDR program. Of these, 17 participated and 18 declined. Baseline characteristics are provided. Participating patients experienced mPEDI of 6.9% (Standard Error [SE], 3.7%), compared with 17.7% (SE, 3.6%) for patients who declined participation. Due to small sample size, this difference (10.8%) did not reach statistical significance (Wilcoxon Rank Sums p-value, 0.15). 30-day mortality did not differ between groups. Mean inpatient days were also lower for patients participating in the program. Additionally, when readmitted, patients participating in RPM experienced a trend toward shorter length of stay and lower rates of intensive care unit utilization. Conclusions: A trend towards decreased burden of inpatient care is evident among patients participating in the DEFeNDR program. Further studies are warranted to assess comparative effectiveness of this model vs usual care.[Table: see text]